In the formation of cataract, many changes in the structure of lens proteins are known to occur. In diabetic cataract, the level of sugar is high. It is not known what effects these sugar molecules have on the structure of lens proteins and whether these effects subsequently lead to cataract formation. In the proposed project, we plan to study in detail the structural changes of these proteins in the presence of sugar, the nature of the interacton between them, and whether the changes are responsible for the opacity of lens. Based on our preliminary results, which indicated structural changes of the lens crystallins, we will systematically explore the nature of interactions between sugar molecules and the proteins, and the change of protein structure brought about by other mechanisms such as sorbitol formation, glycosylation, etc. Methods will include isolation of lens proteins and physicochemical studies of sugar-induced changes on lens protein structure. Techniques such as circular dichroism, fluorescence, and sedimentation studies will be employed. A model approach for studying the relationship between such structural changes and cataract formation will be to study the extent of disulfide bridge formation, or other kinds of aggregation, two common pathways for cataract formation, by using suitable fluorescent probes and sedimentation.